Pathology Lecture 7 Cell Injury I

What is hypoxia, and what are key indicators of hypoxia?

Inadequate oxygenation of tissues. Key indicators include cyanosis, tachycardia, tachypnea, & confusion

What is the difference between hypoxia and ischemia

Hypoxia is more generalized: ↓ OXYGEN in blood

Ischemia is more localized: ↓ BLOOD FLOW to organ/tissues

Give 4 examples of causes of hypoxemia

1. Ventilation defects

2. Perfusion defects

3. Diffusion defects

4. Right-to-Left Shunt

Explain Ventilation Defects

no O2 delivery to alveoli (lungs are perfused but not ventilated)

Explain Perfusion Defects:

absence of blood flow to alveoli ( lungs are ventilated, but not perfused)

ex: pneumonia

Explain Diffusion Defects

Decreased oxygen diffusion through alveolar capillary

(when alveolar space is full of “junk” diffusion is difficult")

ex: pulmonary embolus & infarction

Explain Right-Left-Shunt

Blood bypasses alveoli and there is NO gas exchange

Explain why someone might develop Anemia

If they have a reduce number of healthy RBC’s and reduced hemoglobin concentration

possible cause of Methemoglobinemia

exposure to drugs, especially topical anesthetics

Explain the pathogenesis of methemoglobinemia

1. topical drugs steal an electron from iron turning Ferrous (Fe 2+) into Ferric (Fe 3+)

2. Ferric iron binds to hemoglobin and forms Methemoglobin

3. Methemoglobin DOES NOT bind O2. PaO2 is normal, but SaO2 decreased. oxygen is not delivered to tissues

Effect of methemoglobinemia

cyanosis

Etiology of Carbon Monoxide poisoning

incomplete combustion of carbon containing compounds ex: petroleum, firewood, automobile exhaust

Pathogenesis of CO poisoning

1. CO has 250x greater affinity for binding hemoglobin

2. CO competes with O2 for binding sites. carboxyhemoglobin is formed. ↓ SaO2 saturation (PaO2 is the same)

Effects of CO poisoning

1. headache

2. cherry red skin

3. CT scans of lesion in globus pallidus of basal ganglia

etiology and pathogenesis of circulatory hypoxemia

Etiology: heart failure, shock

Pathogenesis: compromised blood flow. tissues don’t get O2

Describe LEFT sided heart failure

Fluid in alveolar space, shortness of breath

Results in Dyspnea, cyanosis, pulmonary edema and paroxysmal nocturnal dyspnea

blood not pumped to body, so blood backs up into LUNGS

Describe RIGHT sided heart failure

blood is not pumped to lungs, so it backs up in the body

Gravity makes blood accumulate in legs (dependent pitting edema)

Results include prominence of jugular veins, painful hepatomegaly, ascites (fluid buildup in belly)

What is shock? What are some clinical manifestations of shock? (relating to hypoxemia).

persistent hypotention & ↓O2 in tissue, reduced perfusion in organs

manifestations: cold, clammy skin, tachycardia, low urine output

Etiology of Cyanide poisoning

medications (nitroprusside)

combustion of synthetic materials: polyurethane

Pathogenesis of cyanide poisoning

Targets the mitochondria → inactivates cytochrome C oxidase → inhibits oxidative phosphorylation

clinical manifestations of cyanide poisoning

seizures, cardiac arrest, death

skin color goes pink

Summarize the process of Uncouplers of Oxidative Phosphorylation

Uncouplers are lipid soluble → make membrane leaky → H+ gradient is lost → energy is not captured and turns into pure HEAAAT

Examples include Thermogenin (found in hibernating animals) and DNP (dinitophenol)

What areas of the brain are more vulnerable to hypoxia. give an example

Watershed area between two blood supplies

ex: area between the distribution of anterior and middle cerebral arteries

What areas of the heart are more vulnerable to hypoxia.

Subendocardial tissue ; they receive the least amount of oxygen

What areas of the kidney are more vulnerable to hypoxia.

Renal cortex and medulla: specifically the straight portion of the proximal convoluted tubule

Explain the process of reversible cell injury UP UNTIL it becomes irreversible

↓ ATP from oxidative phosphorylation → anaerobic glycolysis used → ↑lactic acid buildup → sodium accumulates inside cell → BLEBS

When is cell injury irreversible

INFLUX of calcium in the cell → leads to lysosomes rupturing and hydrolases leak into cytoplasm

How can you tell that a cell is dead, as it relates to NECROSIS

1. the cell is hypereosinophilic

2. karyopyknosis: nuclear shrinkage & increased basophilia

3. karyrrhexis : nucleus fragmented

4. Karyolysis: nucleus dissolves, leaves behind ghost nucleus.

Describe coagulative necrosis, the types of cells it is most commonly seen in, and its defining features

1. The outline of dead cells is preserved. Denaturation of intracellular enzymes prevents autolysis

2. prevalent in myocardium. kidney, and spleen

3. Features: cytoplasm is hypereosinophilic and cytoplasm looks bright pink with absent nuclei

Describe liquefactive necrosis, the types of cells it may be seen in, and its defining features

1. cells are dissolved by hydrophilic enzymes, tissue becomes liquified.

2. brain or spinal cord and pancreas

3. forms ABSCESS (dead neutrophils), forms a cystic space

Describe caseous necrosis and its defining features

1. Caseous material formed by release of LIPID from cell walls of mycobacterium tuberculosis and fungi after destruction by macrophages

2. Tissue looks yellowish-white, like cheese

Forms granulomas and tissue architecture is obliterated.

What are the two types of fat necrosis, describe them

Enzymatic: located around pancreas. pancreatic lipase causes hydrolysis of triglycerides. FORMS SOAP.

GROSS: Saponification produces chalky white areas around adipose tissues of pancreas and gut

MICROSCOPIC: basophlic staining calcified areas

Traumatic: in breast and thighs, or occurs in other areas of physical injury